The mechanical properties of trabecular muscles from the hearts of 77 rats subjected to aortic arch constriction were compared with those from 77 unoperated and sham-operated control animals at 1, 3, 7, 14, and 28 days after operation. Significant hypertrophy, as evidenced by an increase in left ventricle to body weight ratio, was first seen at three days (
P
< 0.02), reached a maximum of 30 to 40% by seven days (
P
< 0.001), and remained relatively constant throughout the remainder of the experiment. Depression of isotonic shortening velocity and maximum isometric force of trabecular muscles from hypertrophied hearts was first seen at seven days. These changes persisted at 14 and 28 days. When alterations in muscle mechanics due to changes in muscle thickness were taken into consideration, muscles from hypertrophied hearts demonstrated a depressed maximum velocity of shortening (
P
< 0.001), while development of isometric tension was unaltered. The latter appeared to be maintained at least in part by a prolonged contraction time, as reflected by increases in the time to peak isometric tension (
P
< 0.05) and the time to peak "unloaded" isotonic shortening (
P
< 0.001). Resting tension was increased in trabecular muscles from hypertrophied hearts. Tissue hydroxyproline concentration was elevated with hypertrophy. The observed depression in muscle shortening velocity at light loads may be explained by altered contractile state or by increased stiffness of the parallel elastic element.
This review examines the results of vasodilator therapy in patients with chronic regurgitant lesions of the aortic and mitral valves. The analysis includes those studies which provide data on hemodynamic measurements, left ventricular systolic function, ventricular volumes and regurgitant flow. In patients with chronic aortic or mitral regurgitation, the short-term administration of nitroprusside, hydralazine, nifedipine or an angiotensin-converting enzyme (ACE) inhibitor produces salutary hemodynamic effects. The major difference in the response to combined preload and afterload reduction (i.e., nitroprusside) in patients with aortic versus mitral regurgitation was that forward stroke volume generally increased and ejection fraction remained unchanged in mitral regurgitation, whereas ejection fraction generally increased and forward stroke volume remained unchanged in aortic regurgitation. These observations suggest that a reciprocal relation between regurgitant and forward flow characterizes the response to preload and afterload reduction in mitral regurgitation (through a preload-dependent dynamic regurgitant orifice), whereas correction of afterload mismatch dominates the response in aortic regurgitation. In studies of long-term vasodilator therapy in patients with chronic aortic regurgitation, a reduction in left ventricular volumes and regurgitant fraction, with or without an increase in ejection fraction, has been observed during treatment with hydralazine, nifedipine and ACE inhibitors. Patients with the largest, sickest hearts generally benefit the most from treatment with vasoactive drugs. Nonetheless, favorable ventricular remodeling has been reported in asymptomatic patients, and long-term nifedipine use has delayed the need for operation in asymptomatic patients with chronic aortic regurgitation. For patients with chronic mitral regurgitation, definition of the etiology of the lesion is a prerequisite for choosing appropriate therapy. Excluding patients with obstructive hypertrophic cardiomyopathy and mitral valve prolapse, and some with fixed-orifice (i.e., rheumatic) mitral regurgitation, the signal importance of preload reduction suggests that the preferred long-term therapy for symptomatic chronic mitral regurgitation is an ACE inhibitor. There are no long-term studies that support the use of vasodilator therapy in asymptomatic patients with chronic mitral regurgitation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.